The Variations of MER Receptor Tyrosine Kinase and the Development of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is an acquired disease and is caused by significant exposure to noxious particles and gases, mainly by smoking. Meanwhile, it is also apparent that there are susceptible smokers who are prone to develop COPD and “non-susceptible” smokers who never develop clinically significant airflow limitation. In fact, only a small proportion (about 15%–50%) of smokers suffer from the clinically relevant disease,1 which suggests that genetic susceptibility may also affect the development of the disease. In the early 2000s, a cohort study showed the significant risk of airflow limitation in smoking siblings of patients with severe COPD,2 which supports the importance of genetic susceptibility in the development of COPD. At that time, however, the causable genetic variations were not evident except alpha-1 anti-trypsin and some single nucleotide polymorphisms. After a decade, with the progression in methodology, the genome wide association study elucidated many susceptible genes including cholinergic nicotine receptor alpha 3/5 (CHRNA3/5), iron regulatory binding protein 2 (IREB2), hedgehog-interacting protein (HHIP), family with sequence similarity 13, member A (FAM13A), and advanced glycosylation end product-specific receptor (AGER),3 which have been validated in various cohorts. Despite these progressions in genetics, our understanding of the genetic variations in COPD is still insufficient and more studies are required to fully understand their role in the pathogenesis of COPD.